γH2Ax Expression as a Potential Biomarker Differentiating between Low and High Grade Cervical Squamous Intraepithelial Lesions (SIL) and High Risk HPV Related SIL

ObjectiveTo assess the rates of co-infections between human papillomavirus (HPV) and 13 key markers of bacterial vaginosis in cervical samples by multiplex polymerase chain reaction in a population with a high rate of abnormal cytology and a positive HPV test.MethodsThe study included a total of 213 women aged 18–72 years screened using Papanicolaou smears for determining cervical abnormalities and for HPV and bacterial vaginosis by single-target and multiplex polymerase chain reaction.ResultsA total of 83 (39%) women were negative for intraepithelial lesion or malignancy cytology and 130 (61%) had abnormal cytology. HPV-DNA prevalence was 69.9% and bacterial vaginosis was 72.7 %. Co-infections between bacterial vaginosis with HPV-DNA and high-risk HPV were associated with an increased risk for squamous intraepithelial lesions of low-grade cytology and high-grade squamous intraepithelial lesions plus cervical cancer. The most frequent bacterial vaginosis agent was Gardnerella vaginalis (33.8%), and co-infection with HPV-DNA and high-risk HPV increased the risk for squamous intraepithelial lesions of low grade cytology and high-grade squamous intraepithelial lesions plus cervical cancer. Co-infection between Megasphaera type I and high-risk HPV increased the risk for high-grade squamous intraepithelial lesions plus cervical cancer.ConclusionsOur results reinforce the hypothesis that some bacterial vaginosis agents may play a role as co-factors in HPV-mediated cervical carcinogenesis, at least in some populations.

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Role of HPV genotyping in risk assessment among cytology diagnosis categories: analysis of 4562 cases with cytology–HPV cotesting and follow-up biopsies

International Journal of Gynecological Cancer ◽

10.1136/ijgc-2018-000024 ◽

2019 ◽

Vol 29 (2) ◽

pp. 234-241 ◽

Cited By ~ 3

Author(s):

Yimin Ge ◽

Paul Christensen ◽

Eric Luna ◽

Donna Armylagos ◽

Jiaqiong Xu ◽

...

Keyword(s):

High Risk ◽

Positive Predictive Value ◽

Predictive Value ◽

High Grade ◽

Squamous Intraepithelial Lesions ◽

Squamous Cells ◽

Hpv Genotyping ◽

High Risk Hpv ◽

Intraepithelial Lesions ◽

Undetermined Significance

ObjectiveHuman papilloma virus (HPV) detection and genotyping are increasingly used in clinical risk assessment. We aimed to analyze HPV genotyping performance in risk stratification among cytology diagnosis categories.MethodsBetween January 1, 2015 and December 31, 2016, 4562 cases with cytology–HPV co-testing and biopsy follow-up were identified. HPV tests were performed on Cobas (n=3959) or Aptima (n=603) platforms. Of the biopsies, 669 demonstrated high-grade squamous intraepithelial lesions or worse.ResultsPooled high-risk HPV testing had high overall sensitivity (97%) but low specificity (20%) and positive predictive value (20%) for biopsy-confirmed high-grade squamous intraepithelial lesions or worse. HPV16/18 genotyping had considerably improved specificity (81%) and positive predictve value (35%) in predicting high-grade squamous intraepithelial lesions or worse, especially in atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesion categories. Significantly more biopsy-confirmed high-grade squamous intraepithelial lesions or worse were detected by Aptima than Cobas testing, as measured by HPV16/18 (48% vs 33%, p<0.001), non-16/18 high-risk HPV (18% vs 13%, p=0.029), or all high-risk HPV genotypes (27% vs 19%, p<0.001). Aptima genotyping showed a significantly higher positive predictive value than Cobas genotyping for biopsy-confirmed high-grade squamous intraepithelial lesions or worse in the atypical squamous cells of undetermined significance category (47% vs 23%, p<0.05).ConclusionsHPV genotyping was sensitive for biopsy-confirmed high-grade squamous intraepithelial lesions or worse in all cytologic categories, and is particularly valuable in risk evaluation for women with atypical squamous cells of undetermined significance and low-grade squamous intraepithelial lesions. The triaging role was greatly diminished in high-risk lesions (atypical glandular cells, atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesions and high-grade squamous intraepithelial lesions) due to low specificity and positive predictive value. Aptima performance in risk management was superior to Cobas, with significantly higher positive predictive value for biopsy-confirmed high-grade squamous intraepithelial lesions or worse. Our results highlight the importance of careful data interpretation from studies using different HPV testing methods and the need to incorporate HPV E6/E7-mRNA testing into management guidelines.

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